Compositions and methods for the treatment of brain cancers

Abstract

Described herein is an isolated viral particle having a genome that includes open reading frames that encode: Maraba proteins N, P, and L, or variants thereof; as well as Maraba protein M or protein delta 51M, or variants thereof; and a Bahia Grande G protein, a LCMV G protein, or an Ebola G protein. Maraba protein N may have a sequence which includes SEQ ID NO: 1. Maraba protein P may have a sequence which includes SEQ ID NO: 2. Maraba protein L may have a sequence which includes SEQ ID NO: 3. Maraba proteins M and delta 1M may have sequence which include SEQ ID NO: 4 and 5, respectively. Bahia Grande G protein may have a sequence which includes SEQ ID NO: 6. LCMV G protein may have a sequence which includes SEQ ID NO: 7. Ebola G protein may have a sequence which includes SEQ ID NO: 8.

1 . An isolated viral particle having a genome comprising open reading frames that encode:
 a protein having a sequence comprising SEQ ID NO: 1, or a variant thereof;   a protein having a sequence comprising SEQ ID NO: 2, or a variant thereof;   a protein having a sequence comprising SEQ ID NO: 3, or a variant thereof;   a protein having a sequence comprising SEQ ID NO: 4 or 5, or a variant thereof; and   a protein having a sequence comprising SEQ ID NO: 6, 7 or 8.   
     
     
         2 . The isolated viral particle according to  claim 1  wherein the variant of a reference protein is a protein having a sequence which is at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to the sequence of the reference protein, and the variant protein maintains the same biological function as the reference protein. 
     
     
         3 . The isolated viral particle according to  claim 1 , wherein the genome comprises an open reading frame that encodes a protein having a sequence comprising SEQ ID NO: 6. 
     
     
         4 . The isolated viral particle according to  claim 1 , wherein the genome comprises an open reading frame that encodes a protein having a sequence comprising SEQ ID NO: 7. 
     
     
         5 . The isolated viral particle according to  claim 1 , wherein the genome comprises an open reading frame that encodes a protein having a sequence comprising SEQ ID NO: 8. 
     
     
         6 . The isolated viral particle according to  claim 1 , wherein the viral genome comprises open reading frames that encode:
 a protein having a sequence comprising SEQ ID NO: 1;   a protein having a sequence comprising SEQ ID NO: 2;   a protein having a sequence comprising SEQ ID NO: 3;   a protein having a sequence comprising SEQ ID NO: 5; and   a protein having a sequence comprising SEQ ID NO: 7.   
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . A method for treating cancer comprising administering an isolated viral particle according to  claim 1  to a patient having cancer. 
     
     
         34 . The method according to  claim 33  wherein the cancer is a brain cancer. 
     
     
         35 . The method according to  claim 34  wherein the brain cancer is a glioblastoma. 
     
     
         36 . The method according to  claim 33  wherein the isolated viral particle is administered to the patient directly. 
     
     
         37 . The method according to  claim 36  wherein the isolated viral particle is administered directly to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof. 
     
     
         38 . The method according to  claim 37  wherein the isolated viral particle is administered to the patient intrathecally, intravenously, via intracranial injection, or any combination thereof simultaneously or sequentially. 
     
     
         39 . The method according to  claim 33  wherein a cell is infected with the isolated viral particle and the infected cell is administered to the patient. 
     
     
         40 . The method according to  claim 39  wherein the infected cell is administered directly to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof. 
     
     
         41 . The method according to  claim 39  wherein the infected cell is administered to the patient intrathecally, intravenously, via intracranial injection, or any combination thereof simultaneously or sequentially. 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . A kit for the treatment of cancer in a patient, the kit comprising:
 the isolated viral particle according to  claim 1 ; and   instructions for administration of the isolated viral particle to the patient.   
     
     
         50 . The kit according to  claim 49 , wherein the cancer is a brain cancer. 
     
     
         51 . The kit according to  claim 49 , wherein the brain cancer is a glioblastoma. 
     
     
         52 . The kit according to  claim 49  wherein the isolated viral particle is formulated for direct delivery to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof. 
     
     
         53 . The kit according to  claim 52  wherein the isolated viral particle is formulated for administration via intrathecal injection, intravenous injection, intracranial injection, or any combination thereof simultaneously or sequentially. 
     
     
         54 . The kit according to claim  59  wherein the isolated viral particle is formulated for infection of a cell and the cell is for delivery to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof. 
     
     
         55 . The kit according to  claim 54  wherein the cell is for administration via intrathecal injection, intravenous injection, intracranial injection, or any combination thereof simultaneously or sequentially.